Abstract
A range of custom-designed small molecule probes will be synthesised and tested for their efficacy in the selective detection of zinc through a fluorescence switch-on response. Probes that show zinc selectivity in vitro will then be used in cellular models to demonstrate their ability to target specific cellular organelles and to detect “free” zinc in response to stimuli and genetic manipulations that trigger its redistribution.
References
- K. Jobe, C.H. Brennan, M. Motevalli, S.M. Goldup, and M. Watkinson, “Modular ‘click’ sensors for zinc and their application in vivo”, Chem. Commun., 2011, 47, 6036-6038.
- J. Pancholi, D. J. Hodson, K. Jobe, G. A. Rutter, S. M. Goldup and M. Watkinson, “Biologically Targeted Probes for Zn2+: A Diversity Oriented Modular “Click-SNAr-Click” Approach”, Chem. Sci., 2014, 5, 3528-3535.
- N.R. Johnston, et al., “Beta cell hubs dictate pancreatic islet response to glucose”, Cell Metabolism, 2016, 24, 389-401.
- K.M. Taylor, S. Hiscox, R.I. Nicholson, C. Hogstrand and P. Kille, “Protein Kinase CK2 Triggers Cytosolic Zinc Signaling Pathways by Phosphorylation of Zinc Channel ZIP7”, Sci. Signal., 2012, 5, ra11.
- K.M. Taylor, I. Muraina, D. Brethour, G. Schmitt-Ulms, T. Nimmanon, S. Ziliotto, P. Kille and C. Hogstrand, “Zinc transporter ZIP10 forms a heteromer with ZIP6 which regulates embryonic development and cell migration”, Biochem. J., 2016, 473, 2531-2544.